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1.
JAMA Psychiatry ; 80(9): 895-904, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37378972

RESUMO

Importance: Tobacco smoking drives markedly elevated cardiovascular disease risk and preventable death in persons with serious mental illness, and these risks are compounded by the high prevalence of overweight/obesity that smoking cessation can exacerbate. Guideline-concordant combined pharmacotherapy and behavioral smoking cessation treatment improves abstinence but is not routinely offered in community settings, particularly to those not seeking to quit smoking immediately. Objective: To determine the effectiveness of an 18-month pharmacotherapy and behavioral smoking cessation intervention incorporating weight management and support for physical activity in adults with serious mental illness interested in quitting smoking within 1 or 6 months. Design, Setting, and Participants: This was a randomized clinical trial conducted from July 25, 2016, to March 20, 2020, at 4 community health programs. Adults with serious mental illness who smoked tobacco daily were included in the study. Participants were randomly assigned to intervention or control, stratified by willingness to try to quit immediately (within 1 month) or within 6 months. Assessors were masked to group assignment. Interventions: Pharmacotherapy, primarily varenicline, dual-form nicotine replacement, or their combination; tailored individual and group counseling for motivational enhancement; smoking cessation and relapse prevention; weight management counseling; and support for physical activity. Controls received quitline referrals. Main Outcome and Measures: The primary outcome was biochemically validated, 7-day point-prevalence tobacco abstinence at 18 months. Results: Of the 298 individuals screened for study inclusion, 192 enrolled (mean [SD] age, 49.6 [11.7] years; 97 women [50.5%]) and were randomly assigned to intervention (97 [50.5%]) or control (95 [49.5%]) groups. Participants self-identified with the following race and ethnicity categories: 93 Black or African American (48.4%), 6 Hispanic or Latino (3.1%), 90 White (46.9%), and 9 other (4.7%). A total of 82 participants (42.7%) had a schizophrenia spectrum disorder, 62 (32.3%) had bipolar disorder, and 48 (25.0%) had major depressive disorder; 119 participants (62%) reported interest in quitting immediately (within 1 month). Primary outcome data were collected in 183 participants (95.3%). At 18 months, 26.4% of participants (observed count, 27 of 97 [27.8%]) in the intervention group and 5.7% of participants (observed count, 6 of 95 [6.3%]) in the control group achieved abstinence (adjusted odds ratio [OR], 5.9; 95% CI, 2.3-15.4; P < .001). Readiness to quit within 1 month did not statistically significantly modify the intervention's effect on abstinence. The intervention group did not have significantly greater weight gain than the control group (mean weight change difference, 1.6 kg; 95% CI, -1.5 to 4.7 kg). Conclusions and Relevance: Findings of this randomized clinical trial showed that in persons with serious mental illness who are interested in quitting smoking within 6 months, an 18-month intervention with first-line pharmacotherapy and tailored behavioral support for smoking cessation and weight management increased tobacco abstinence without significant weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT02424188.


Assuntos
Transtorno Depressivo Maior , Abandono do Hábito de Fumar , Abandono do Uso de Tabaco , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Dispositivos para o Abandono do Uso de Tabaco , Aumento de Peso
2.
J Am Geriatr Soc ; 71(7): 2208-2218, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36821761

RESUMO

BACKGROUND: To assess whether vitamin D3 supplementation attenuates the decline in daily physical activity in low-functioning adults at risk for falls. METHODS: Secondary data analyses of STURDY (Study to Understand Fall Reduction and Vitamin D in You), a response-adaptive randomized clinical trial. Participants included 571 adults aged 70 years and older with baseline serum 25(OH)D levels of 10-29 ng/mL and elevated fall risk, who wore a wrist accelerometer at baseline and at least one follow-up visit and were randomized to receive: 200 IU/day (control), 1000, 2000, or 4000 IU/day of vitamin D3 . Objective physical activity quantities and patterns (total daily activity counts, active minutes/day, and activity fragmentation) were measured for 7-days, 24-h/day, in the free-living environment using the Actigraph GT9x over up to 24-months of follow-up. RESULTS: In adjusted models, physical activity quantities declined (p < 0.001) and became more fragmented, or "broken up", (p = 0.017) over time. Supplementation with vitamin D3 did not attenuate this decline. Changes in physical activity were more rapid among those with baseline serum 25(OH)D <20 ng/mL compared to those with baseline 25(OH)D levels of 20-29 ng/mL (time*baseline 25(OH)D, p < 0.05). CONCLUSION: In low-functioning older adults with serum 25(OH)D levels 10-29 ng/mL, vitamin D3 supplementation of 1000 IU/day or higher did not attenuate declines in physical activity compared with 200 IU/day. Those with baseline 25(OH)D <20 ng/mL showed accelerated declines in physical activity. Alternative interventions to supplementation are needed to curb declines in physical activity in older adults with low serum 25(OH)D.


Assuntos
Suplementos Nutricionais , Deficiência de Vitamina D , Humanos , Idoso , Idoso de 80 Anos ou mais , Vitamina D , Vitaminas/uso terapêutico , Colecalciferol/uso terapêutico , Exercício Físico , Método Duplo-Cego
3.
Med Sci Sports Exerc ; 55(2): 281-288, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36170549

RESUMO

INTRODUCTION: Low physical activity is a criterion of phenotypic frailty defined as an increased state of vulnerability to adverse health outcomes. Whether disengagement from daily all-purpose physical activity is prospectively associated with frailty and possibly modified by chronic inflammation-a pathway often underlying frailty-remains unexplored. METHODS: Using the Study to Understand Fall Reduction and Vitamin D in You data from 477 robust/prefrail adults (mean age = 76 ± 5 yr; 42% women), we examined whether accelerometer patterns (activity counts per day, active minutes per day, and activity fragmentation [broken accumulation]) were associated with incident frailty using Cox proportional hazard regression. Baseline interactions between each accelerometer metric and markers of inflammation that include interleukin-6, C-reactive protein, and tumor necrosis factor-alpha receptor 1 were also examined. RESULTS: Over an average of 1.3 yr, 42 participants (9%) developed frailty. In Cox regression models adjusted for demographics, medical conditions, and device wear days, every 30 min·d -1 higher baseline active time, 100,000 more activity counts per day, and 1% lower activity fragmentation was associated with a 16% ( P = 0.003), 13% ( P = 0.001), and 8% ( P < 0.001) lower risk of frailty, respectively. No interactions between accelerometer metrics and baseline interleukin-6, C-reactive protein, or tumor necrosis factor-alpha receptor 1 were detected (interaction P > 0.06 for all). CONCLUSIONS: Among older adults who are either robust or prefrail, constricted patterns of daily physical activity (i.e., lower total activity minutes and counts, and higher activity fragmentation) were prospectively associated with higher risk of frailty but not modified by frailty-related chronic inflammation. Additional studies, particularly trials, are needed to understand if this association is causal.


Assuntos
Fragilidade , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Interleucina-6 , Proteína C-Reativa , Incidência , Fator de Necrose Tumoral alfa , Inflamação
4.
Nutrients ; 13(8)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34444833

RESUMO

Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures; reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean ± standard deviation (SD) age of 60 ± 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 ± 5 kg/m2, and SU was 5.6 ± 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m2 (95% confidence interval (CI): -1.5, -0.4) and metformin reduced BMI by 0.6 kg/m2 (95% CI: -1.1, -0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: -0.04, 0.5); these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction; however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.


Assuntos
Terapia Comportamental , Metformina/uso terapêutico , Ácido Úrico/sangue , Redução de Peso , Idoso , Índice de Massa Corporal , Feminino , Gota , Humanos , Masculino , Maryland , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico
5.
Diabetes Care ; 44(7): 1462-1471, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34006565

RESUMO

OBJECTIVE: To determine the longer-term effects of metformin treatment and behavioral weight loss on gut microbiota and short-chain fatty acids (SCFAs). RESEARCH DESIGN AND METHODS: We conducted a 3-parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n = 121) to either 1) metformin (up to 2,000 mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n = 114), 6 months (n = 109), and 12 months (n = 105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. RESULTS: Of the 121 participants, 79% were female and 46% were Black, and the mean age was 60 years. Only metformin treatment significantly altered microbiota composition. Compared with control, metformin treatment increased amplicon sequence variants for Escherichia (confirmed as Escherichia coli by metagenomic sequencing) and Ruminococcus torques and decreased Intestinibacter bartlettii at both 6 and 12 months and decreased the genus Roseburia, including R. faecis and R. intestinalis, at 12 months. Effects were similar in comparison of the metformin group with the behavioral weight loss group. Metformin versus control also increased butyrate, acetate, and valerate at 6 months (but not at 12 months). Behavioral weight loss versus control did not significantly alter microbiota composition but did increase acetate at 6 months (but not at 12 months). Increases in acetate were associated with decreases in fasting insulin. Additional whole-genome metagenomic sequencing of a subset of the metformin group showed that metformin altered 62 metagenomic functional pathways, including an acetate-producing pathway and three pathways in glucose metabolism. CONCLUSIONS: Metformin, but not behavioral weight loss, impacted gut microbiota composition at 6 months and 12 months. Both metformin and behavioral weight loss altered circulating SCFAs at 6 months, including increasing acetate, which correlated with lower fasting insulin. Future research is needed to elucidate whether the gut microboime mediates or modifies metformin's health effects.


Assuntos
Microbioma Gastrointestinal , Metformina , Adulto , Ácidos Graxos Voláteis , Fezes , Feminino , Humanos , Metformina/uso terapêutico , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Redução de Peso
6.
J Clin Endocrinol Metab ; 106(10): e4179-e4191, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-33884414

RESUMO

CONTEXT: Higher levels of insulin-like growth factor-1 (IGF-1) are associated with increased risk of cancers and higher mortality. Therapies that reduce IGF-1 have considerable appeal as means to prevent recurrence. DESIGN: Randomized, 3-parallel-arm controlled clinical trial. INTERVENTIONS AND OUTCOMES: Cancer survivors with overweight or obesity were randomized to (1) self-directed weight loss (comparison), (2) coach-directed weight loss, or (3) metformin treatment. Main outcomes were changes in IGF-1 and IGF-1:IGFBP3 molar ratio at 6 months. The trial duration was 12 months. RESULTS: Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average body mass index was 35 kg/m2; mean IGF-1 was 72.9 (SD, 21.7) ng/mL; and mean IGF1:IGFBP3 molar ratio was 0.17 (SD, 0.05). At 6 months, weight changes were -1.0% (P = 0.07), -4.2% (P < 0.0001), and -2.8% (P < 0.0001) in self-directed, coach-directed, and metformin groups, respectively. Compared with the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/mL, P = 0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, P = 0.011) at 3 months. The significant decrease of IGF-1 remained in participants with obesity at 6 months (mean difference in change: -7.2 ng/mL; 95% CI: -13.3 to -1.1), but not in participants with overweight (P for interaction = 0.045). There were no significant differences in changes between the coach-directed and self-directed groups. There were no differences in outcomes at 12 months. CONCLUSIONS: In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.


Assuntos
Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Metformina/uso terapêutico , Manejo da Obesidade/métodos , Obesidade/terapia , Índice de Massa Corporal , Sobreviventes de Câncer , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Tutoria , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Resultado do Tratamento , Redução de Peso/fisiologia
7.
J Hypertens ; 39(3): 447-452, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33060449

RESUMO

OBJECTIVES: Averaging multiple blood pressure (BP) measurements is recommended for hypertension (HTN) screening but can be impractical, especially in resource-constrained settings. We aimed to explore the implications of fewer BP measurements on BP classification and subsequent cardiovascular disease (CVD) risk. METHODS: We studied 8905 middle-aged participants without diagnosed HTN and quantified misclassified HTN (≥140/90 mmHg) by simplified BP approaches (e.g. single 1st BP, single 2nd BP, mainly 1st but 2nd BP if 1st was in a certain range) vs. the reference standard of the average of 2nd and 3rd BP. We also assessed CVD risk related to HTN status. RESULTS: There were 823 participants classified as HTN by the standard approach. With single 1st BP, 2.8% of non-HTN were overidentified as HTN, and 18.3% of HTN were identified as not having HTN. The corresponding estimates with single 2nd BP were 2.1 and 6.4%. Similar estimates were seen when 2nd BP was used if 1st BP at least 130/80 (1.9 and 8.1%), with only 27.8% requiring 2nd BP. Two thousand, one hundred and seventy-eight CVD cases were documented in this population over 30 years. HTN by either the standard approach or any of the simplified approaches conferred higher CVD risk vs. consistent no HTN by both approaches. CONCLUSION: In those without diagnosed HTN, a simplified BP measurement approach using the 2nd BP only when the 1st BP is at least 130/80 could reduce the total number of BP measurements by more than 50%, identify HTN with limited misclassification (2-8%), and predict CVD risks reasonably well.


Assuntos
Aterosclerose , Hipertensão , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Pressão Sanguínea , Determinação da Pressão Arterial , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Programas de Rastreamento , Pessoa de Meia-Idade
8.
JAMA Netw Open ; 3(6): e207247, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32530472

RESUMO

Importance: Persons with serious mental illness have a cardiovascular disease mortality rate more than twice that of the overall population. Meaningful cardiovascular risk reduction requires targeted efforts in this population, who often have psychiatric symptoms and cognitive impairment. Objective: To determine the effectiveness of an 18-month multifaceted intervention incorporating behavioral counseling, care coordination, and care management for overall cardiovascular risk reduction in adults with serious mental illness. Design, Setting, and Participants: This randomized clinical trial was conducted from December 2013 to November 2018 at 4 community mental health outpatient programs in Maryland. The study recruited adults with at least 1 cardiovascular disease risk factor (hypertension, diabetes, dyslipidemia, current tobacco smoking, and/or overweight or obesity) attending the mental health programs. Of 398 participants screened, 269 were randomized to intervention (132 participants) or control (137 participants). Data collection staff were blinded to group assignment. Data were analyzed on the principle of intention to treat, and data analysis was performed from November 2018 to March 2019. Interventions: A health coach and nurse provided individually tailored cardiovascular disease risk reduction behavioral counseling, collaborated with physicians to implement appropriate risk factor management, and coordinated with mental health staff to encourage attainment of health goals. Programs offered physical activity classes and received consultation on serving healthier meals; intervention and control participants were exposed to these environmental changes. Main Outcomes and Measures: The primary outcome was the change in the risk of cardiovascular disease from the global Framingham Risk Score (FRS), which estimates the 10-year probability of a cardiovascular disease event, from baseline to 18 months, expressed as percentage change for intervention compared with control. Results: Of 269 participants randomized (mean [SD] age, 48.8 [11.9] years; 128 men [47.6%]), 159 (59.1%) had a diagnosis of schizophrenia or schizoaffective disorder, 67 (24.9%) had bipolar disorder, and 38 (14.1%) had major depressive disorder. At 18 months, the primary outcome, FRS, was obtained for 256 participants (95.2%). The mean (SD) baseline FRS was 11.5% (11.5%) (median, 8.6%; interquartile range, 3.9%-16.0%) in the intervention group and 12.7% (12.7%) (median, 9.1%; interquartile range, 4.0%-16.7%) in the control group. At 18 months, the mean (SD) FRS was 9.9% (10.2%) (median, 7.7%; interquartile range, 3.1%-12.0%) in the intervention group and 12.3% (12.0%) (median, 9.7%; interquartile range, 4.0%-15.9%) in the control group. Compared with the control group, the intervention group experienced a 12.7% (95% CI, 2.5%-22.9%; P = .02) relative reduction in FRS at 18 months. Conclusions and Relevance: An 18-month behavioral counseling, care coordination, and care management intervention statistically significantly reduced overall cardiovascular disease risk in adults with serious mental illness. This intervention provides the means to substantially reduce health disparities in this high-risk population. Trial Registration: ClinicalTrials.gov Identifier: NCT02127671.


Assuntos
Doenças Cardiovasculares , Transtornos Mentais , Comportamento de Redução do Risco , Adulto , Pressão Sanguínea , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus , Feminino , Humanos , Hipertensão , Lipídeos/sangue , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Obesidade , Fatores de Risco , Resultado do Tratamento
9.
Am J Clin Nutr ; 111(3): 545-554, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31927581

RESUMO

BACKGROUND: Short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate) are produced by microbial fermentation of fiber in the colon. Evidence is lacking on how high-fiber diets that differ in macronutrient composition affect circulating SCFAs. OBJECTIVES: We aimed to compare the effects of 3 high-fiber isocaloric diets differing in %kcal of carbohydrate, protein, or unsaturated fat on circulating SCFAs. Based on previous literature, we hypothesized that serum acetate, the main SCFA in circulation, increases on all high-fiber diets, but differently by macronutrient composition of the diet. METHODS: OmniHeart is a randomized crossover trial of 164 men and women (≥30 y old); 163 participants with SCFA data were included in this analysis. We provided participants 3 isocaloric high-fiber (∼30 g/2100 kcal) diets, each for 6 wk, in random order: a carbohydrate-rich (Carb) diet, a protein-rich (Prot) diet (protein predominantly from plant sources), and an unsaturated fat-rich (Unsat) diet. We used LC-MS to quantify SCFA concentrations in fasting serum, collected at baseline and the end of each diet period. We fitted linear regression models with generalized estimating equations to examine change in ln-transformed SCFAs from baseline to the end of each diet; differences between diets; and associations of changes in SCFAs with cardiometabolic parameters. RESULTS: From baseline, serum acetate concentrations were increased by the Prot (ß: 0.24; 95% CI: 0.12, 0.35), Unsat (ß: 0.21; 95% CI: 0.10, 0.33), and Carb (ß: 0.12; 95% CI: 0.01, 0.24) diets; between diets, only Prot compared with Carb was significant (P = 0.02). Propionate was decreased by the Carb (ß: -0.10; 95% CI: -0.16, -0.03) and Unsat (ß: -0.10; 95% CI: -0.16, -0.04) diets, not the Prot diet; between diet comparisons of Carb vs. Prot (P = 0.006) and Unsat vs. Prot (P = 0.002) were significant. The Prot diet increased butyrate (ß: 0.05; 95% CI: 0.00, 0.09) compared with baseline, but not compared with the other diets. Increases in acetate were associated with decreases in insulin and glucose; increases in propionate with increases in leptin, LDL cholesterol, and blood pressure; and increases in butyrate with increases in insulin and glucose, and decreases in HDL cholesterol and ghrelin (Ps < 0.05). CONCLUSIONS: Macronutrient composition of high-fiber diets affects circulating SCFAs, which are associated with measures of appetite and cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT00051350.


Assuntos
Carboidratos da Dieta/metabolismo , Fibras na Dieta/metabolismo , Proteínas Alimentares/metabolismo , Gorduras Insaturadas/metabolismo , Ácidos Graxos Voláteis/sangue , Adulto , Apetite , Pressão Sanguínea , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Carboidratos da Dieta/análise , Fibras na Dieta/análise , Proteínas Alimentares/análise , Gorduras Insaturadas/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
PLoS One ; 15(1): e0224977, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940353

RESUMO

BACKGROUND: An elevated gamma gap (>4 g/dL), the difference between serum total protein and albumin, can trigger testing for chronic infections or monoclonal gammopathy, despite a lack of evidence supporting this clinical threshold. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2014, gamma gap was derived in three subpopulations based on availability of testing for human immunodeficiency virus (HIV; N = 25,680), hepatitis C (HCV; N = 45,134), and monoclonal gammopathy of unknown significance (MGUS; N = 6,118). Disease status was confirmed by HIV antibody and Western blot, HCV RNA test, or electrophoresis with immunofixation. Sensitivity, specificity, and likelihood ratios were calculated for different gamma gap thresholds. Area under the curve (AUC) was used to assess performance and cubic splines were used to characterize the relationship between the gamma gap and each disease. RESULTS: Mean gamma gaps of participants with HIV, HCV, or MGUS ranged from 3.4-3.8 g/dL. The AUC was 0.80 (95%CI: 0.75,0.85) for HIV, 0.74 (0.72,0.76) for HCV, and 0.64 (0.60,0.69) for MGUS. An elevated gamma gap of over 4 g/dL corresponded to sensitivities of 39.3%, 19.0%, and 15.4% and specificities of 98.4%, 97.8%, and 95.4% for HIV, HCV, and MGUS, respectively. A higher prevalence of all three diseases was observed at both low and high gamma gaps. DISCUSSION: An elevated gamma gap of 4 g/dL is insensitive for HIV, HCV, or MGUS, but has a high specificity for HIV and HCV, suggesting that the absence of an elevated gamma gap does not rule out HIV, HCV, or MGUS. Conversely, an elevated gap may justify further testing for HIV and HCV, but does not justify electrophoresis in the absence of additional clinical information.


Assuntos
Proteínas Sanguíneas , Infecções por HIV/sangue , Hepatite C/sangue , Gamopatia Monoclonal de Significância Indeterminada/sangue , Albumina Sérica , Adulto , Idoso , Feminino , HIV/patogenicidade , Infecções por HIV/virologia , Hepacivirus/patogenicidade , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/patologia
11.
Hypertension ; 73(4): 785-793, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30776971

RESUMO

Apparent treatment-resistant hypertension (ATRH) is highly prevalent and associated with cardiovascular disease risk in patients with chronic kidney disease. We analyzed the association of inflammatory biomarkers with ATRH and its complications in patients with chronic kidney disease. ATRH was defined as blood pressure ≥140/90 mm Hg while taking ≥3 antihypertensive medications or blood pressure <140/90 mm Hg while taking ≥4 medications. Analyses included 1359 CRIC study (Chronic Renal Insufficiency Cohort) participants with ATRH and 2008 hypertensive participants without. Logistic regression was used to examine cross-sectional associations of inflammatory biomarkers and ATRH adjusting for demographic, lifestyle, and clinical risk factors and treatments. Cox proportional hazards models were used to assess the impact of inflammatory biomarkers on associations of ATRH with composite cardiovascular disease and mortality beyond conventional risk factors. Multivariable-adjusted odds ratio (95% CI) of ATRH for the highest tertile versus the lowest tertile of inflammatory biomarker levels was 1.29 (95% CI, 1.05-1.59) for IL (interleukin)-6, 1.49 (95% CI, 1.20-1.85) for TNF-α (tumor necrosis factor-α), and 0.77 (95% CI, 0.63-0.95) for TGF-ß (transforming growth factor-ß). High-sensitivity CRP (C-reactive protein), fibrinogen, IL-1ß, and IL-1 receptor antagonist were not significantly associated with ATRH. Adding inflammatory biomarkers to Cox models did not attenuate the significant association of ATRH with cardiovascular disease and mortality. Our findings show higher levels of IL-6 and TNF-α and lower levels of TGF-ß were independently associated with odds of ATRH. Targeting specific inflammatory pathways may improve blood pressure control in patients with chronic kidney disease.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Citocinas/sangue , Taxa de Filtração Glomerular/fisiologia , Hipertensão/epidemiologia , Inflamação/sangue , Insuficiência Renal Crônica/epidemiologia , Adulto , Idoso , Biomarcadores/sangue , Comorbidade , Estudos Transversais , Resistência a Medicamentos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
12.
Clin Trials ; 15(2): 130-138, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29361843

RESUMO

BACKGROUND/AIMS: Despite widespread Internet adoption, online advertising remains an underutilized tool to recruit participants into clinical trials. Whether online advertising is a cost-effective method to enroll participants compared to other traditional forms of recruitment is not known. METHODS: Recruitment for the Survivorship Promotion In Reducing IGF-1 Trial, a community-based study of cancer survivors, was conducted from June 2015 through December 2016 via in-person community fairs, advertisements in periodicals, and direct postal mailings. In addition, "Right Column" banner ads were purchased from Facebook to direct participants to the Survivorship Promotion In Reducing IGF-1 Trial website. Response rates, costs of traditional and online advertisements, and demographic data were determined and compared across different online and traditional recruitment strategies. Micro-trials optimizing features of online advertisements were also explored. RESULTS: Of the 406 respondents to our overall outreach efforts, 6% (24 of 406) were referred from online advertising. Facebook advertisements were shown over 3 million times (impressions) to 124,476 people, which resulted in 4401 clicks on our advertisement. Of these, 24 people ultimately contacted study staff, 6 underwent prescreening, and 4 enrolled in the study. The cost of online advertising per enrollee was $794 when targeting a general population versus $1426 when accounting for strategies that specifically targeted African Americans or men. By contrast, community fairs, direct mail, or periodicals cost $917, $799, or $436 per enrollee, respectively. Utilization of micro-trials to assess online ads identified subtleties (e.g. use of an advertisement title) that substantially impacted viewer interest in our trial. CONCLUSION: Online advertisements effectively directed a relevant population to our website, which resulted in new enrollees in the Survivorship Promotion In Reducing IGF-1 Trial at a cost comparable to traditional methods. Costs were substantially greater with online recruitment when targeting under-represented populations, however. Additional research using online micro-trial tools is needed to evaluate means of more precise recruitment to improve yields in under-represented groups. Potential gains from faster recruitment speed remain to be determined.


Assuntos
Publicidade/métodos , Sobreviventes de Câncer , Redes Sociais Online , Seleção de Pacientes , Mídias Sociais/estatística & dados numéricos , Adulto , Publicidade/economia , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Mídias Sociais/economia
13.
Front Psychiatry ; 9: 786, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30800079

RESUMO

Persons with serious mental illness (SMI) comprise a high-risk group for cardiovascular disease (CVD)-related mortality with rates at least twice those of the overall US. Potentially modifiable CVD risk behaviors (tobacco smoking, obesity, physical inactivity, unhealthy diet) and risk factors (hypertension, diabetes, dyslipidemia) are all markedly elevated in persons with SMI. Evaluations of programs implementing integrated medical care into specialty mental health settings have not shown meaningful effects on CVD risk factor reduction. Rigorously tested, innovative interventions are needed to address the large burden of CVD risk in populations with SMI. In this article, we describe the design of a comprehensive 18-month intervention to decrease CVD risk that we are studying in a randomized clinical trial in a community mental health organization with psychiatric rehabilitation programs. The individual-level intervention incorporated health behavior coaching and care coordination/care management to address all seven CVD risk behaviors and risk factors, and is delivered by a health coach and nurse. If successful, the intervention could be adopted within current integrated care models and significantly improve the physical health of persons with SMI.

14.
Kidney Int ; 91(1): 196-203, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28029431

RESUMO

Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers.


Assuntos
Falência Renal Crônica/urina , Túbulos Renais/patologia , Insuficiência Renal Crônica/urina , Acetilglucosaminidase/urina , Idoso , Albuminúria/urina , Biomarcadores/urina , Creatinina/urina , Progressão da Doença , Proteínas de Ligação a Ácido Graxo/urina , Feminino , Seguimentos , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Falência Renal Crônica/epidemiologia , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
15.
Am J Kidney Dis ; 68(6): 853-861, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27519166

RESUMO

BACKGROUND: There are established guidelines for recommended dietary intake for hypertension treatment and cardiovascular disease prevention. Evidence is lacking for effective dietary patterns for kidney disease prevention. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Atherosclerosis Risk in Communities (ARIC) Study participants with baseline estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m2 (N=14,882). PREDICTOR: The Dietary Approaches to Stop Hypertension (DASH) diet score was calculated based on self-reported dietary intake of red and processed meat, sweetened beverages, sodium, fruits, vegetables, whole grains, nuts and legumes, and low-fat dairy products, averaged over 2 visits. OUTCOMES: Cases were ascertained based on the development of eGFRs<60mL/min/1.73m2 accompanied by ≥25% eGFR decline from baseline, an International Classification of Diseases, Ninth/Tenth Revision code for a kidney disease-related hospitalization or death, or end-stage renal disease from baseline through 2012. RESULTS: 3,720 participants developed kidney disease during a median follow-up of 23 years. Participants with a DASH diet score in the lowest tertile were 16% more likely to develop kidney disease than those with the highest score tertile (HR, 1.16; 95% CI, 1.07-1.26; P for trend < 0.001), after adjusting for sociodemographics, smoking status, physical activity, total caloric intake, baseline eGFR, overweight/obese status, diabetes status, hypertension status, systolic blood pressure, and antihypertensive medication use. Of the individual components of the DASH diet score, high red and processed meat intake was adversely associated with kidney disease and high nuts, legumes, and low-fat dairy products intake was associated with reduced risk for kidney disease. LIMITATIONS: Potential measurement error due to self-reported dietary intake and lack of data for albuminuria. CONCLUSIONS: Consuming a DASH-style diet was associated with lower risk for kidney disease independent of demographic characteristics, established kidney risk factors, and baseline kidney function. Healthful dietary patterns such as the DASH diet may be beneficial for kidney disease prevention.


Assuntos
Hipertensão/dietoterapia , Nefropatias/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
16.
BMC Nephrol ; 17(1): 70, 2016 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-27391484

RESUMO

BACKGROUND: Replacing carbohydrate with protein acutely increases glomerular filtration rate (GFR) but is associated with faster, long-term kidney disease progression. The effects of carbohydrate type (i.e. glycemic index, GI) on kidney function are unknown. METHODS: We conducted an ancillary study of a randomized, crossover feeding trial in overweight/obese adults without diabetes or kidney disease (N = 163). Participants were fed each of four healthy, DASH-like diets for 5 weeks, separated by 2-week washout periods. Weight was kept constant. The four diets were: high GI (GI ≥65) with high %carb (58 % kcal) (reference diet), low GI (≤45) with low %carb (40 % kcal), low GI with high %carb; and high GI with low %carb. Plasma was collected at baseline and after each feeding period. Study outcomes were cystatin C, ß2-microglobulin (ß2M), and estimated GFR based on cystatin C (eGFRcys). RESULTS: Mean (SD) age was 52 (11) years; 52 % were women; 50 % were black. At baseline, mean (SD) cystatin C, ß2M, and eGFRcys were 0.8 (0.1) mg/L, 1.9 (0.4) mg/L, and 104 (16) mL/min/1.73 m(2). Compared to the high GI/high %carb diet, reducing GI, %carb, or both increased eGFRcys by 1.9 mL/min/1.73 m(2) (95 % CI: 1.1, 2.7; P < 0.001), 3.0 mL/min/1.73 m(2) (1.9, 4.0; P < 0.001), and 4.5 mL/min/1.73 m(2) (3.5, 5.4; P < 0.001), respectively. Increases in eGFRcys from reducing GI were significantly associated with increases in eGFRcys from reducing %carb (P < 0.001). Results for cystatin C and ß2M reflected eGFRcys. CONCLUSIONS: Reducing GI increased GFR. Reducing %carb by increasing calories from protein and fat, also increased GFR. Future studies on GI should examine the long-term effects of this increase in GFR on kidney injury markers and clinical outcomes. TRIAL REGISTRATION: Clinical Trials.gov, number: NCT00608049 (first registered January 23, 2008).


Assuntos
Carboidratos da Dieta/administração & dosagem , Taxa de Filtração Glomerular , Índice Glicêmico , Rim/fisiologia , Obesidade/fisiopatologia , Adulto , Creatinina/sangue , Creatinina/urina , Estudos Cross-Over , Cistatina C/sangue , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Microglobulina beta-2/sangue
17.
Arthritis Rheumatol ; 68(5): 1281-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26636424

RESUMO

OBJECTIVE: The effects of carbohydrates on plasma uric acid levels are a subject of controversy. We determined the individual and combined effects of carbohydrate quality (the glycemic index) and quantity (the proportion of total daily energy [percentage of carbohydrates]) on uric acid levels. METHODS: We conducted a randomized, crossover trial of 4 different diets in overweight or obese adults without cardiovascular disease (n = 163). Participants consumed each of 4 diets over a 5-week period, each of which was separated by a 2-week washout period. Body weight was kept constant. The 4 diets were high glycemic index (≥65) with high percentage of carbohydrates (58% kcal), low glycemic index (≤45) with low percentage of carbohydrates (40% kcal), low glycemic index with high percentage of carbohydrates, and high glycemic index with low percentage of carbohydrates. Plasma uric acid levels were measured at baseline and after completion of each 5-week period for comparison between the 4 diets. RESULTS: Of the 163 study participants, 52% were women and 50% were non-Hispanic African American subjects; their mean age was 52.6 years, and their mean ± SD uric acid level was 4.7 ± 1.2 mg/dl. Reducing the glycemic index lowered uric acid levels when the percentage of carbohydrates was low (-0.24 mg/dl; P < 0.001) or high (-0.17 mg/dl; P < 0.001). Reducing the percentage of carbohydrates marginally increased the uric acid level only when the glycemic index was high (P = 0.05). The combined effect of lowering the glycemic index and increasing the percentage of carbohydrates was -0.27 mg/dl (P < 0.001). This effect was observed even after adjustment for concurrent changes in kidney function, insulin sensitivity, and products of glycolysis. CONCLUSION: Reducing the glycemic index lowers uric acid levels. Future studies should examine whether reducing the glycemic index can prevent gout onset or flares.


Assuntos
Dieta com Restrição de Carboidratos , Carboidratos da Dieta , Índice Glicêmico , Obesidade/sangue , Ácido Úrico/sangue , Adulto , Negro ou Afro-Americano , Glicemia/metabolismo , Colesterol/sangue , HDL-Colesterol/sangue , Estudos Cross-Over , Cistatina C/metabolismo , Feminino , Hispânico ou Latino , Humanos , Insulina/sangue , Resistência à Insulina , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/sangue , Sobrepeso/metabolismo , Triglicerídeos/sangue , População Branca
18.
PLoS One ; 10(12): e0143494, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26629820

RESUMO

BACKGROUND: The difference between total serum protein and albumin, i.e. the gamma gap, is a frequently used clinical screening measure for both latent infection and malignancy. However, there are no studies defining a positive gamma gap. Further, whether it is an independent risk factor of mortality is unknown. METHODS AND FINDINGS: This study examined the association between gamma gap, all-cause mortality, and specific causes of death (cardiovascular, cancer, pulmonary, or other) in 12,260 participants of the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. Participants had a comprehensive metabolic panel measured, which was linked with vital status data from the National Death Index. Cause of death was based on ICD10 codes from death certificates. Analyses were performed with Cox proportional hazards models adjusted for mortality risk factors. The mean (SE) age was 46 (0.3) years and the mean gamma gap was 3.0 (0.01) g/dl. The population was 52% women and 10% black. During a median follow-up period of 4.8 years (IQR: 3.3 to 6.2 years), there were 723 deaths. The unadjusted 5-year cumulative incidences across quartiles of the gamma gap (1.7-2.7, 2.8-3.0, 3.1-3.2, and 3.3-7.9 g/dl) were 5.7%, 4.2%, 5.5%, and 7.8%. After adjustment for risk factors, participants with a gamma gap of ≥3.1 g/dl had a 30% higher risk of death compared to participants with a gamma gap <3.1 g/dl (HR: 1.30; 95%CI: 1.08, 1.55; P = 0.006). Gamma gap (per 1.0 g/dl) was most strongly associated with death from pulmonary causes (HR 2.22; 95%CI: 1.19, 4.17; P = 0.01). CONCLUSIONS: The gamma gap is an independent risk factor for all-cause mortality at values as low as 3.1 g/dl (in contrast to the traditional definition of 4.0 g/dl), and is strongly associated with death from pulmonary causes. Future studies should examine the biologic pathways underlying these associations.


Assuntos
Albuminas/metabolismo , Proteínas Sanguíneas/metabolismo , Doenças Cardiovasculares/mortalidade , Pneumopatias/mortalidade , Mortalidade/tendências , Neoplasias/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Causas de Morte , Feminino , Humanos , Incidência , Pneumopatias/epidemiologia , Pneumopatias/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/metabolismo , Inquéritos Nutricionais , Fatores de Risco , Estados Unidos
19.
Br J Nutr ; 113(9): 1396-409, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-25850683

RESUMO

Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures of performance for the prediction model were calculated using cross-validation. For the prediction model of fruit, vegetable and juice intake, the root mean squared error (RMSE) was 258.0 g, the correlation between observed and predicted intake was 0.78 and the mean difference between observed and predicted intake was - 1.7 g (limits of agreement: - 466.3, 462.8 g). For the prediction of fruit and vegetable intake (excluding juices), the RMSE was 201.1 g, the correlation was 0.65 and the mean bias was 2.4 g (limits of agreement: -368.2, 373.0 g). The prediction models which include the biomarkers and subject characteristics may be used to estimate average intake at the group level and to investigate the ranking of individuals with regard to their intake of fruit and vegetables when validating questionnaires that measure intake.


Assuntos
Biomarcadores/sangue , Dieta , Frutas , Verduras , Adolescente , Adulto , Ácido Ascórbico/sangue , Índice de Massa Corporal , Carotenoides/sangue , Criptoxantinas/sangue , Feminino , Ácido Fólico/sangue , Humanos , Luteína/sangue , Licopeno , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem , Zeaxantinas/sangue , beta Caroteno/sangue
20.
Am J Kidney Dis ; 65(2): 267-74, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25311702

RESUMO

BACKGROUND: Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). STUDY DESIGN: Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. SETTING & PARTICIPANTS: 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008. PREDICTOR: Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. OUTCOMES: Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. MEASUREMENTS: Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). RESULTS: There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. LIMITATIONS: Urine NGAL was measured only once. CONCLUSIONS: Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.


Assuntos
Proteínas de Fase Aguda/urina , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/urina , Lipocalinas/urina , Proteínas Proto-Oncogênicas/urina , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/urina , Adulto , Idoso , Biomarcadores/urina , Doenças Cardiovasculares/diagnóstico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco
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